The Physicians' Health Study (PHS) is a randomized trial of aspirin and beta-carotene in the prevention of cardiovascular mortality and cancer incidence, conducted among 22,071 U.S. male physicians aged 40-84 years. As part of the trial, blood samples were collected prior to randomization from 14,916 participants, and have been stored at -82 degrees. Using a case-control design, we now propose th analyse these specimens for levels of retinol, beta-carotene, retinol-binding protein, vitamins E and B6, selenium, lipids, and fatty acids. If is likely that any chemopreventive effect of beta-carotene will be modified by baseline blood levels, reflecting intake from dietary sources. It the anti-cancer activity of beta-carotene operates chiefly or solely among those who initially have low blood levels, the present trial may have insufficient power to detect this effeect, because the target group with low beta-carotene levels would not be identifiable. However, the proposed analyses will provide the opportunity to observe this effect. The primary objective of the proposed study is, therefore, to enhance the power and interpretability of the PHS findings. For maximal utilization of these specimens, we will also test a number of hypotheses relating blood levels of various nutrients to risk of subsequent cancer and myocardial infarction. We will analyze specimens for all cases of invazive cancer and documented myocardial infarction, and an equal number of age-matched controls. Current evidence suggests that a number of these nutrients may have important interactions with beta-carotene as well as among one other. The case-control approach and the multiple analyses provide and effecient means to increase the value of the PHS and test a number of nutrition-related hypotheses of potential public health importance using blood samples that were collected at considerable expense, and protected with great care.